Age of blood and recipient factors determine the severity of transfusion-related acute lung injury (TRALI)

Abstract

Introduction: Critical care patients frequently receive blood transfusions. Some reports show an association between aged or stored blood and increased morbidity and mortality, including the development of transfusion-related acute lung injury (TRALI). However, the existence of conflicting data endorses the need for research to either reject this association, or to confirm it and elucidate the underlying mechanisms.

Methods: Twenty-eight sheep were randomised into two groups, receiving saline or lipopolysaccharide (LPS). Sheep were further randomised to also receive transfusion of pooled and heat-inactivated supernatant from fresh (Day 1) or stored (Day 42) non-leucoreduced human packed red blood cells (PRBC) or an infusion of saline. TRALI was defined by hypoxaemia during or within two hours of transfusion and histological evidence of pulmonary oedema. Regression modelling compared physiology between groups, and to a previous study, using stored platelet concentrates (PLT). Samples of the transfused blood products also underwent cytokine array and biochemical analyses, and their neutrophil priming ability was measured in vitro.

Results: TRALI did not develop in sheep that first received saline-infusion. In contrast, 80% of sheep that first received LPS-infusion developed TRALI following transfusion with "stored PRBC." The decreased mean arterial pressure and cardiac output as well as increased central venous pressure and body temperature were more severe for TRALI induced by "stored PRBC" than by "stored PLT." Storage-related accumulation of several factors was demonstrated in both "stored PRBC" and "stored PLT", and was associated with increased in vitro neutrophil priming. Concentrations of several factors were higher in the "stored PRBC" than in the "stored PLT," however, there was no difference to neutrophil priming in vitro.

Conclusions: In this in vivo ovine model, both recipient and blood product factors contributed to the development of TRALI. Sick (LPS infused) sheep rather than healthy (saline infused) sheep predominantly developed TRALI when transfused with supernatant from stored but not fresh PRBC. "Stored PRBC" induced a more severe injury than "stored PLT" and had a different storage lesion profile, suggesting that these outcomes may be associated with storage lesion factors unique to each blood product type. Therefore, the transfusion of fresh rather than stored PRBC may minimise the risk of TRALI.

Figure 1

Representative histology. Representative haemotoxylin and eosin stained lung sections analysed histologically for pulmonary oedema. These range from no pulmonary oedema (A) through to mild (B), moderate (C) and severe (D) pulmonary oedema. Neutrophils were identified by morphological assessment and are indicated by the blue arrows (E and F). In contrast to sham sheep (E), there was widespread evidence of neutrophil infiltration in the lungs of LPS-stored sheep (F). LPS, lipopolysaccharide.

Figure 2

Haemodynamic and respiratory changes. Averaged data over 30-minute periods for each of the six groups of sheep. The first event (either saline or LPS) was infused from 0 to 30 minutes and the second event (either saline, "fresh PRBC" or "stored PRBC") was infused from 90 to 150 minutes. The left column represents sheep receiving saline-infusion as a first event (that is, sham, saline-fresh and saline-stored groups), and the right column represents sheep receiving LPS-infusion as a first event (that is, LPS-control, LPS-fresh and LPS-stored groups). Dashed lines at O₂sat = 90% and PaO₂ = 125 mmHg (FiO₂ was 40%, therefore PaO₂/FiO₂ = 300) represent clinical cut-offs for hypoxaemia. LPS-stored sheep developed lower MAP, CO, PaO₂, and O₂ sat as well as higher PAP relative to sham sheep. Also, saline-stored sheep displayed increased PAP relative to sham sheep. # P < 0.05 vs. sham group using a two-way ANOVA with Bonferroni's multiple comparisons adjustment. LPS-stored sheep developed lower static pulmonary compliance, CO, PaO₂, and O₂ sat as well as higher PAP relative to the LPS-control group. * P < 0.05 vs. LPS-control using a two-way ANOVA with Bonferroni's multiple comparisons adjustment. ANOVA, analysis of variance; CO, continuous cardiac output; FiO₂, fraction of inspired oxygen; "fresh PRBC," pooled heat-inactivated supernatant from Day 1 human PRBC; LPS, lipopolysaccharide; MAP, mean arterial pressure; O₂sat, oxygen saturation; PaO₂, arterial partial pressure of oxygen; PAP, pulmonary artery pressure; "stored PRBC," pooled heat-inactivated supernatant from Day 42 human PRBC; TRALI, transfusion-related acute lung injury.

Figure 3

Neutrophil priming ability. Ability to prime fMLP-induced human neutrophil respiratory burst function is shown as mean of n = 4 experiments. Error bars indicate SEM. Both "stored PRBC" and "stored PLT" display increased ability to prime fMLP-induced neutrophil respiratory burst than the equivalent fresh product. There was no difference between the ability of "stored PRBC" and "stored PLT" to prime fMLP-induced neutrophil respiratory burst. # P < 0.001 "stored PLT" vs. "fresh PLT" using a one-way ANOVA with Bonferroni's multiple comparisons adjustment. * P < 0.001 "stored PRBC" vs. "fresh PRBC" using a one-way ANOVA with Bonferroni's multiple comparisons adjustment. ns P > 0.05 "stored PRBC" vs. "stored PLT" using a one-way ANOVA with Bonferroni's multiple comparisons adjustment. ANOVA, analysis of variance; fMLP, N-formylmethionyl-leucyl-phenylalanine; "fresh PLT", pooled heat-inactivated supernatant from Day 1 non-leucoreduced human platelet concentrates; "fresh PRBC", pooled heat-inactivated supernatant from Day 1 non-leucoreduced human packed red blood cell concentrates; min, minute; O₂^-, superoxide anion; PAF, platelet activating factor; PLT, platelet concentrate, PRBC packed red blood cells; "stored PLT", pooled heat-inactivated supernatant from Day 5 non-leucoreduced human platelet concentrates; "stored PRBC", pooled heat-inactivated supernatant from day 42 non-leucoreduced human packed red blood cell concentrates; SEM, standard error of the mean.